Solvent-free processing, system and methods

ABSTRACT

Disclosed is a process for purifying one or more chemical constituents from plant matter using extraction with a fluid that is not a solvent, for example, with a vegetable oil. The extracted chemical constituents may then optionally be further processed by heating in order to induce desired chemical transformations. The extracted chemical constituents are also processed by concentrating at reduced pressure, for example, by distillation.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of Ser. No. 14/537,341, filed Nov. 10,2014, which claims priority to U.S. Provisional Patent Application No.61/902,388, filed Nov. 11, 2013, the entire contents of which areincorporated herein by reference.

FIELD OF THE DISCLOSURE

The present disclosure relates to systems and methods for solvent-freeprocessing of plant materials. The system and methods may use othermaterials, in place of a solvent, such as oil or an ionic liquid, forextracting plant material or for further extraction of a plant extract,followed by purification by distillation, optionally with heat-inducedchemical transformation of natural products in the plant material. Theheat-induced chemical transformation can include decarboxylation.

BACKGROUND OF THE INVENTION

Natural products encompass chemicals and chemical compositions derivedfrom plants, animals, fungi, and microorganisms (see, e.g., Newman andCragg (2012) J. Natural Products, 75:311-335). Natural products includetaxanes, such as paclitaxel, which is renowned for use in treatingcancer (Heinig and Jennewein (2009) African J. Biotech. 8:1370-1385).Natural products also include terpenes, which include aromaticcompounds, such as limonene, menthol, eugenol, and beta-caryophyllene,which are used in foods and perfumes. Analogues of natural products havealso found commercial use, and these include Warfarin, an analogue ofthe natural product, coumarin (Link (1959) Circulation. 19:97-107), andfingolimod, derived from a natural product made by the fungus Isariasinclairii, and which is used to treat multiple sclerosis (Chiba andAdachi (2012) Future Med. Chem. 4:771-781).

Administered cannabinoids, as provided by non-purified sources or bypartially purified sources, have found use in reducing the symptoms ofvarious diseases. For example, administered cannabinoids have been foundto reduce the spasticity, neuropathic pain, and tremors of multiplesclerosis (Leussink et al (2012) Ther. Adv. Neurol. Disord. 5:255-266;Lakhan and Rowland (2009) BMC Neurology. 9:59 (6 pages)). Moreover,cannabinoids can relieve chronic neuropathic pain (Ware et al (2010)Canadian Med. Assoc. J. 182:E694-E701; Grant et al (2012) Open NeurologyJ. 6:18-25; Lynch and Campbell (2011) Brit. J. Clin. Pharmacol.72:735-744). The present disclosure fulfills an unmet need by providingconcentrated preparations of purified cannabinoids that do not containsolvent, and that were not prepared using any solvent.

Some methods of preparing chemical compounds from plant material areknown in the art e.g., U.S. Pat. No. 7,700,368, to Flockhart et al.;U.S. Pat. No. 8,846,409, issued Sep. 30, 2014, to Flockhart et al.; andEuropean Patent Serial No. 1 536 810 B1 to Whittle et al.; the contentsof all of which are incorporated by reference herein in their entirety).Methods of decarboxylating cannabinoids are also known (see U.S. PatentPublication Serial No. 2012/0046352 to Hospodor, the contents of whichare incorporated by reference herein in their entirety).

SUMMARY

Briefly stated, the present disclosure comprises a process for purifyingchemicals from plant matter using extraction with a fluid that is not asolvent, for example, with a vegetable oil. The extracted chemicals arethen further processed by heating in order to induce a chemicaltransformation, which may be decarboxylation of extracted carboxylicacids. The extracted chemicals are also processed by concentrating atreduced temperature and pressures, for example, by distillation.

Systems and methods of the present disclosure are particularly usefulfor purifying chemicals such as tetrahydrocannabinolic acid (THCA),cannabidiolic acid (CBDA), and cannabigerolic acid (CBGA); anddecarboxylating them to tetrahydrocannabinol (THC), cannabidiol (CBD),and cannabigerol (CBG), respectively.

A solvent is a substance that dissolves a solute, resulting in asolution. A solution has a single phase wherein the solvent and soluteform complexes. This situation differs from non-solution mixtureswherein the compounds are insoluble, such that a residue remains. In asolution, the compounds are uniformly distributed at a molecular level,and no residue remains. A compound may be defined as a non-solvent inrelation to another compound that cannot dissolve into it. For example,canola oil is a non-solvent of THC. The present disclosure includes theuse of a variety of non-solvents, such as oils or ionic liquids.

The present disclosure provides a method for purifying one or morechemical constituents from plant matter comprising the steps of: (i)contacting the plant matter with a non-solvent; (ii) allowing chemicalconstituents from the plant matter to dissociate from the plant matterand to disperse into the non-solvent, thereby producing extracted plantmatter and producing a non-solvent enriched in the chemicalconstituents; (iii) separating the extracted plant matter from thenon-solvent enriched in the chemical constituents; and (iv) volatilizingat least one of the chemical constituents by one or more of heat,vacuum, or heat and vacuum, and (v) collecting the volatilized chemicalconstituents, wherein the collected volatilized chemical constituents isdefined as the final product.

Also provided is the above method, wherein the non-solvent that isenriched in chemical constituents contains one or more of6,10,14-trimethyl-2-pentadecanone, octacosane, hentriacontane, andeicosane, wherein the content of 6,10,14-trimethyl-2-pentadecanone,octacosane, hentriacontane, and eicosane, is defined as 100 percent(100%), and wherein the content in the final product of each of the oneor more of 6,10,14-trimethyl-2-pentadecanone, octacosane,hentriacontane, and eicosane, is less than 50%.

In another aspect, the content in the final product of6,10,14-trimethyl-2-pentadecanone is less than 80%, less than 70%, lessthan 60%, less than 50%, less than 40%, less than 30%, less than 20%,less than 10%, less than 5%, less than 2%, less than 1%, and so on.

In another aspect, the content in the final product of octacosane isless than 80%, less than 70%, less than 60%, less than 50%, less than40%, less than 30%, less than 20%, less than 10%, less than 5%, lessthan 2%, less than 1%, and so on.

In another aspect, the content in the final product of hentriacontane isless than 80%, less than 70%, less than 60%, less than 50%, less than40%, less than 30%, less than 20%, less than 10%, less than 5%, lessthan 2%, less than 1%, and so on.

In another aspect, the content in the final product of eicosane, is lessthan 80%, less than 70%, less than 60%, less than 50%, less than 40%,less than 30%, less than 20%, less than 10%, less than 5%, less than 2%,less than 1%, and so on.

What is further contemplated is the above method, wherein thenon-solvent enriched in the chemical constituents comprisesheat-decarboxylatable chemical constituents; that further includes thestep of exposing to heat conditions that are sufficient to provokeheat-induced decarboxylation of at least some of theheat-decarboxylatable chemical constituents.

Also embraced is the above method that further includes the step ofexposing the one or more chemical constituents to heat conditions thatare sufficient to provoke heat-induced decarboxylation of at least someof the heat-decarboxylatable chemical constituents, wherein the heatconditions is more than 100° C., more than 98° C., more than 96° C.,more than 94° C., more than 92° C., more than 90° C., more than 88° C.,more than 86° C., more than 84° C., more than 82° C., more than 80° C.,and so on.

Additionally, what is provided is the above method wherein thevolatilization is conducted at a temperature that is more than 100degrees C., more than 98° C., more than 96° C., more than 94° C., morethan 92° C., more than 90° C., more than 88° C., more than 86° C., morethan 84° C., more than 82° C., more than 80° C., and so on.

Also provided is the above method, wherein the non-solvent that isenriched in the chemical constituents is not processed by contactingwith an inert matrix.

Also provided is the above method that does not comprise adding solventin Step (i).

Also provided is the above method, wherein the chemical constituentscomprise one or more cannabinoids.

Also provided is the above method, wherein the chemical constituents donot comprise a cannabinoid.

Also provided is the above method, wherein the plant matter is acannabaceae, or is derived from a cannabaceae.

Also provided is the above method, wherein the non-solvent that isenriched in the chemical constituents comprises a first chemicalconstituent and a second constituent, and wherein the step ofvolatilizing results in a volatilized fraction, and also results in theseparation of the first chemical constituent from the second chemicalconstituent, wherein the volatilized fraction is relatively enriched inthe first chemical constituent and relatively depleted in the secondchemical constituent.

Also provided is the above method, wherein the non-solvent that isenriched in the chemical constituents comprises a first chemicalconstituent and a second constituent, wherein the step of volatilizingresults in a volatilized fraction, and also results in the separation ofthe first chemical constituent from the second chemical constituent,wherein the volatilized fraction is relatively enriched in the firstchemical constituent and relatively depleted in the second chemicalconstituent, and wherein the non-solvent that is enriched in thechemical constituents contains heat-decarboxylatable chemicalconstituents, and wherein the step of volatilization results inheat-induced decarboxylation of less than about 5% of theheat-decarboxylatable chemical constituents.

In yet another aspect, what is provided is the above method, wherein thenon-solvent that is enriched in the chemical constituents comprises afirst chemical constituent and a second constituent, and wherein thestep of volatilizing results in a volatilized fraction, and also resultsin the separation of the first chemical constituent from the secondchemical constituent, wherein the volatilized fraction is relativelyenriched in the first chemical constituent and relatively depleted inthe second chemical constituent, and wherein the non-solvent that isenriched in the chemical constituents contains heat-decarboxylatablechemical constituents, and wherein the step of volatilization results inheat-induced decarboxylation of less than about 10% of theheat-decarboxylatable chemical constituents.

Moreover, what is provided is the above method, wherein the step ofseparating the extracted plant matter from the non-solvent that isenriched in the chemical constituents comprises one or more of (a)Centrifuging or filtering; or (b) Drawing hot gas through thenon-solvent that is enriched in chemical constituents in order tovolatilize and remove at least some of the chemical constituents.

Also provided is the above method, wherein the step of separating theextracted plant matter from the non-solvent that is enriched in thechemical constituents comprises drawing hot gas through the non-solventthat is enriched in chemical constituents in order to volatilize andremove at least some of the chemical constituents, followed bycondensing the volatilized and removed chemical constituents to generateand collect a composition that comprises one or more condensedconstituents. Also provided is the above method, wherein the step ofexposing the chemical constituent to heat conditions that are sufficientto provoke heat-induced decarboxylation of at least one of theheat-decarboxylatable chemical constituent is conducted: during Step(ii); during Step (iii) with the proviso that Step (iii) comprisesdrawing hot gas through the non-solvent that is enriched in compound orchemical; or after Step (iii) but before Step (iv). In another aspect,the heat conditions are sufficient to provoke decarboxylation of atleast two of the heat-decarboxylatable chemical constituents, at leastthree of the heat-decarboxylatable chemical constituents, at leastwherein Step (iv) comprises a partial vacuum that increasesvolatilization of at least some of the chemical constituents from thenon-solvent.

Also provided is the above method, wherein Steps (i-iv) are conductedcontinuously, and wherein the rate of each step is individuallycontrolled to allow Steps (i-iv) to allow continuous operation, and toprevent substantial accumulation of partially processed chemicalconstituents from in between any given two adjacent two steps.

Also provided is the above method, wherein the plant matter comprisescannabaceae that is one or more of dried, chopped, ground, or powdered.

Also provided is the above method, wherein extraction with thenon-solvent is batchwise.

Also provided is the above method, wherein extraction with thenon-solvent is continuous and not batchwise.

Further provided is the above method, wherein the non-solvent comprisesa vegetable oil, fruit oil, seed oil, nut oil, fish oil, wax oil, or amixture of said oils.

Also provided is the above method, wherein the non-solvent comprises avegetable oil that is canola oil, sunflower oil, safflower oil, or cornoil, or a mixture of one or more of said vegetable oils.

Also provided is the above method, wherein the non-solvent comprises anut oil that is peanut oil, walnut oil, or almond oil, or a mixture ofone or more of said nut oils.

Also provided is the above method, wherein the non-solvent comprises anionic liquid, such as tributylmethylammonium methyl sulfate, or animidazolium salt such as 1-butyl-3-methylimidazolium chloride.

Also provided is the above method, wherein the step of extracting doesnot include any solvent in an amount (concentration) sufficient to beeffective in promoting extraction of the chemical constituents from theplant matter.

In system embodiments, what is provided is a system that is capable ofcarrying out a method for purifying one or more chemical constituentsfrom plant matter comprising the steps of: (i) Contacting the plantmatter with a non-solvent; (ii) Allowing chemical constituents from theplant matter to dissociate from the plant matter and to disperse intothe non-solvent, thereby producing extracted plant matter and producinga non-solvent enriched in the chemical constituents; (iii) Separatingthe extracted plant matter from the non-solvent enriched in the chemicalconstituents; and (iv) Volatilizing at least one of the chemicalconstituents by one or more of heat, vacuum, or heat and vacuum, and (v)Collecting the volatilized chemical constituents, wherein the collectedvolatilized chemical constituents is defined as the final product;wherein the non-solvent enriched in the chemical constituents comprisesheat-decarboxylatable chemical constituents; that further includes thestep of exposing to heat conditions that are sufficient to provokeheat-induced decarboxylation of at least some of theheat-decarboxylatable chemical constituents, wherein the systemcomprises an extractor, a vacuum pump, an evaporator, a non-solvent foruse in extracting plant matter, and a heating unit that is configuredfor heat-induced decarboxylation of a decarboxylatable chemicalconstituents. Also provided is the above system, wherein the non-solventcomprises a vegetable oil. Also provided is the above system, whereinthe heating unit comprises one of: (i) a hot gas that is drawn through acomposition comprising the chemical constituents and the non-solvent;(ii) a heating unit that is configured to heat the chemical constituentsand volatilize evaporable chemical constituents, but that does not heatthe chemical constituents by drawing hot gas through the compositioncomprising the chemical constituents and the non-solvent.

The following specifically concerns cannabinoids. What is provided is amethod for purifying one or more cannabinoids from plant mattercomprising the steps of: (i) Contacting the plant matter with anon-solvent; (ii) Allowing cannabinoids from the plant matter todissociate from the plant matter and to disperse into the non-solvent,thereby producing extracted plant matter and producing a non-solventthat is enriched in the cannabinoids; (iii) Separating the extractedplant matter from the non-solvent that is enriched in the chemicalconstituent; and (iv) Concentrating the cannabinoids by distilling.

What is provided is the above method, that further includes the step ofexposing the one or more cannabinoids to heat conditions that aresufficient to provoke heat-induced decarboxylation of at least some ofthe decarboxylatable cannabinoids. What is also provided is the abovemethod, that excludes solvent from Step (i). What is provided is theabove method, wherein the plant matter is derived from a cannabaceae.What is embraced is the above method, wherein the step of separating theextracted plant matter from the non-solvent that is enriched in thecannabinoids comprises one or more of: (a) Centrifuging or filtering; or(b) Drawing hot gas through the non-solvent that is enriched in chemicalconstituent in order to volatilize and remove at least some of thecannabinoids.

What is further contemplated is the above method, wherein the step ofexposing the cannabinoid to heat conditions that are sufficient toprovoke heat-induced decarboxylation of at least some of thedecarboxylatable cannabinoids is conducted: during Step (ii); duringStep (iii) with the proviso that Step (iii) comprises drawing hot gasthrough the non-solvent that is enriched in cannabinoid; or after Step(iii) but before Step (iv). Further provided is the above method,wherein Step (iv) comprises rotary evaporation or bulk distillation.Also embraced is the above method, wherein Step (iv) does not comprisebulk distillation.

Additionally contemplated is the above method, wherein Step (iv)comprises a partial vacuum that increases volatilization of at leastsome of the chemical constituents from the non-solvent. Also provided isthe above method, wherein Steps (i-iv) are conducted continuously, andwherein the rate of each step is individually controlled to allow Steps(i-iv) to allow continuous operation, and to prevent substantialaccumulation of partially processed chemical constituents fromaccumulating in between any given two adjacent two steps.

Also provided is the above method, wherein the plant matter comprisescannabaceae that is one or more of dried, chopped, ground, or, powdered.Further embraced is the above method, wherein extraction with thenon-solvent is batchwise. Also provided is the above method, whereinextraction with the non-solvent is continuous and not batchwise.

What is further provided is the above method, wherein the non-solventcomprises a vegetable oil, fruit oil, seed oil, or a nut oil. Providedis the above method, wherein the non-solvent comprises a vegetable oilthat is canola oil, sunflower oil, safflower oil, or corn oil, or amixture of one or more of said vegetable oils. Provided is the abovemethod, wherein the non-solvent comprises a nut oil that is peanut oil,walnut oil, or almond oil, or a mixture of one or more of said nut oils.Also provided is the above method, wherein the non-solvent comprises anionic liquid, such as tributylmethylammonium methyl sulfate. Alsoprovided is the above method, wherein the step of extracting does notinclude any solvent in an amount (concentration) sufficient to beeffective in promoting extraction of the chemical constituent from theplant matter.

In systems embodiments, what is provided is a system that is capable ofcarrying out the above method, wherein the system comprises anextractor, a vacuum pump, an evaporator, a non-solvent, and a heatingunit that is configured for heat-induced decarboxylation of adecarboxylatable chemical constituent. Also provided is the abovesystem, wherein the non-solvent is a vegetable oil. Further provided isthe above system, wherein the heating unit comprises one of: (i) a hotgas that is drawn through a composition comprising the chemicalconstituent and the non-solvent; (ii) a heating unit that is configuredto heat the chemical constituent and volatilize evaporable chemicalconstituents, but that does not heat the chemical constituents bydrawing hot gas through the composition comprising the chemicalconstituent and the non-solvent.

Methods of continuous operation that prevent accumulation ofpartially-processed, or partially-purified chemical constituent at anygiven intermediate step are provided, as follows. What is embraced isthe above method, wherein Steps (i-iv) are conducted continuously, andwherein the rate of each step is individually controlled to allow Steps(i-iv) to allow continuous operation, and to prevent substantialaccumulation of partially processed chemical constituents fromaccumulating in between any given two adjacent two steps.

Also embraced is the above method, wherein Steps (i-v) are conductedcontinuously, and wherein the rate of each step is individuallycontrolled to allow Steps (i-v) to allow continuous operation, and toprevent substantial accumulation of partially processed chemicalconstituents from accumulating in between any given two adjacent twosteps.

In embodiments, the present disclosure also provides the above methodwherein the plant matter comprises one or more of dried cannabis,powdered cannabis, chopped cannabis, or ground cannabis. Also providedis the above method, wherein extraction with the non-solvent isbatchwise. Also contemplated is the above method, wherein extractionwith the non-solvent is continuous and not batchwise. Further providedis the above method, wherein the non-solvent comprises a vegetable oilor a nut oil. Additionally provided is the above method, wherein thenon-solvent comprises a vegetable oil that is canola oil, sunflower oil,safflower oil, or corn oil, or a mixture of one or more of saidvegetable oils. In yet another aspect, what is provided is the abovemethod, wherein the non-solvent comprises a nut oil that is peanut oil,walnut oil, or almond oil, or a mixture of one or more of said nut oils.Also provided is the above method, wherein the non-solvent comprises anionic liquid, such as tributylmethylammonium methyl sulfate. Alsoprovided is the above method, wherein the step of extracting does notinclude any solvent in an amount (concentration) sufficient to beeffective in promoting extraction of cannabinoids from the plant matter.

In a system embodiment, what is provided is a system that is capable ofcarrying out the above method, wherein the system comprises anextractor, an evaporator, a non-solvent, and a heating unit that isconfigured for heat-induced decarboxylation of cannabinoids. Alsoprovided is the above system, wherein the non-solvent is a vegetableoil. Also provided is the above method, wherein the non-solventcomprises an ionic liquid. Moreover, what is embraced is the abovesystem, wherein the heating unit that is configured for heat-induceddecarboxylation of cannabinoids comprises one of: (i) a hot gas that isdrawn through a composition comprising cannabinoids and a non-solvent;(ii) a heating unit that does not heat the cannabinoids by drawing hotgas through the composition comprising cannabinoids and a non-solvent.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a method of purifying a chemical compound from plantmatter.

FIG. 2 shows a method of purifying a chemical compound from plantmatter.

FIG. 3 shows a method of purifying a chemical compound from plantmatter.

FIG. 4 shows experimental results of a decarboxylation trial accordingto methods of the present disclosure.

DETAILED DESCRIPTION

The present disclosure encompasses all possible combinations of theabove embodiments, and encompasses all possible disclosures of eachindependent claim with its dependent claims. For example, what isencompassed is an invention that is the combination of Claim 1+Claim 2;or the combination of Claim 1+Claim 2+Claim 3; or the combination ofClaim 1+Claim 3+Claim 4; or the combination of Claim 1+Claim 2+Claim3+Claim 4; and the like.

As used herein, including the appended claims, the singular forms ofwords such as “a,” “an,” and “the” include their corresponding pluralreferences unless the context clearly dictates otherwise. All referencescited herein are incorporated by reference to the same extent as if eachindividual publication, patent, and published patent application, aswell as figures and drawings in said publications and patent documents,was specifically and individually indicated to be incorporated byreference.

The terms “adapted to,” “configured for,” and “capable of,” mean thesame thing. Where more than one of these terms are used in a claim set,it is the case that each and every one of these terms, as they mightoccur, means, “capable of.”

Without implying any limitation, the term “chemical constituent”encompasses chemicals and compounds. “Compound” preferably refers to amolecular entity or complex such as a glycolipid (covalent complex ofoligosaccharide and a lipid), a glycopeptide, a lipoprotein, glutamicoxaloacetate amino transferase (complex of an enzyme and pyridoxalphosphate). Where the term “compound” is used, the complex may be anon-covalent complex, it may be a covalent complex, or it may be acomplex that has both covalent and non-covalent character. The term“compound” can also be used to the combination of an ionized chemicalwith its counter ion.

Different botanical products produce different chemical constituents. Itis often desirable to extract wanted chemical constituents from unwantedbulk plant material to provide a more well defined, often standardized,extract of components that can be more easily utilized in furtherprocessing steps or directly by mammals via various consumption methods.It is always undesirable to utilize extraction methods that may leaveunwanted chemical residues in the extract that could limit humanconsumption potentials. Furthermore, the use of typical solvents likealcohols and alkanes, ethanol and hexane, pose additional flammabilityand handling hazards which increase the economic burden of theprocessing method. Certain chemical constituents of interest may bequite polar and could lend towards extraction with water, of whichstevia glycosides would be an excellent example, but most often thedesired constituents are non-polar and are best extracted via the use ofalkanes as the extraction solvent. The present disclosure utilizesvegetable oils as an inexpensive, safe handling and highly efficientmeans of extracting desired chemical constituents from botanicals ofinterest.

FIGS. 1-3 show methods of purifying a chemical compound from plantmatter according to the present disclosure. The methods described can beperformed in the absence of a solvent. The embodiments shown in thefigures are non-limiting examples of the methods and processes describedherein, and may be modified according to other embodiments describedherein. The individual steps of FIGS. 1-3 can be interchanged orcombined in accordance with the present disclosure.

FIG. 1 shows a method 100 of purifying a chemical compound. The methodcan be performed in the absence of a solvent. The method involves anoptional first step 110 of distilling a non-solvent to remove a volatilefraction. The non-solvent can comprise an oil such as a plant oil,vegetable oil, seed oil, nut oil, canola oil, fish oil, or the like. Inother embodiments, the non-solvent comprises an ionic liquid, such astributylmethylammonium methyl sulfate. In step 120, the non-solvent,which may have had a volatile fraction removed in step 110, is contactedto plant matter. The plant matter can comprise cannabaceae or aderivative thereof. A chemical compound from the plant matter isextracted into the non-solvent in step 130, producing (1) a mixturecomprising a non-solvent enriched in the chemical compound and (2) plantmatter residue. The chemical compound may be a carboxylic acid. It mayalso or alternatively be a cannabinoid. Extraction may involve mixing,stirring, agitating, vortexing, or the like. It may also involveheating. Optionally, the plant matter residue can be further processedin step 135 by contacting it with an aliquot of the non-solvent, andthen repeating the extraction step 130. Optionally the mixture can becooled before proceeding.

The enriched non-solvent and the plant matter residue are separated instep 140. Separating the materials may comprise straining, filtering, orcentrifuging. For example, the non-solvent and plant matter mixture canbe placed in a food-grade mesh, such as a nylon straining bag, andpressed in a mechanical press, such as a wine press, to separateenriched oil product from plant matter residue byproduct. Alternatively,or in addition, part or all of the mixture can be separated using anauger-type oil extractor. The separating step 140 can be repeatedmultiple times to extract the most enriched oil product.

Step 150 involves volatilizing the chemical compound out of the enrichednon-solvent to produce a purified chemical compound. Volatilizing maycomprise exposure to heat, vacuum, or partial vacuum. In a preferredembodiment, heating comprises elevating the temperature over 100 degreesC. In embodiments where the extracted chemical compound is a carboxylicacid, the purified chemical compound may comprise a decarboxylatedcompound.

FIG. 2 shows a method 200 according to the present disclosure, whereinmore than one chemical compound can be purified. The method 200 mayembody all of the limitations embodied in the description of the method100 in FIG. 1. The method 200 further comprises step 220, which involvesextracting two or more chemical compounds into the non-solvent toproduce a mixture comprising (1) a non-solvent enriched in more than onechemical compound and (2) plant matter residue.

In step 240, one or more chemical compounds are volatilized out of theenriched non-solvent to produce one or more purified chemical compounds.The properties of the compounds may be such that they volatilize atdifferent temperatures. In that case, one compound may be volatilized ata lower temperature, and the second compound may subsequently bevolatilized at a higher temperature, leading to two separate purifiedcompounds. The purified compounds may be mixed together or be keptseparate. In alternative embodiments, the two compounds may bevolatilized at the same time, using a temperature at which bothvolatilize. The step 240 may result in a volatilized fraction that isenriched in one compound but not the other. Or it may result in avolatilized fraction that is enriched in both compounds. In embodiments,the method 200 may involve more than two compounds with different or thesame volatilization temperatures.

FIG. 3 shows another method 300 of purifying a chemical compound. Themethod 300 involves decarboxylating the chemical compound to produce adecarboxylated compound in step 340. In some embodiments, step 340occurs in conjunction with a volatilization step 350. In otherembodiments, steps 340 and 350 occur separately. The present disclosureencompasses methods wherein step 340 occurs before step 350, as well asmethods wherein step 350 occurs before step 340. Decarboxylation mayinvolve heating, such as elevating the temperature of the chemicalcompound to 100 degrees C. or more. Heating can be by any method knownin the art. For example, heating may comprise drawing hot gas throughthe enriched non-solvent. In other embodiments heating may comprisecontacting the non-solvent to a hot surface, such as a surface with atemperature differential of 70 degrees C. compared to the startingtemperature of the non-solvent. Heating may also involve the use of anoven or a heat exchanger.

The procedures and processes described below provide a non-limiting andexemplary disclosure of the methods.

Extracting and Filtering

A non-solvent such as canola oil can be purified before use inextracting plant matter, as follows. Canola oil is distilled, and thedistillate is set aside or discarded. The non-volatile fraction isretained, for use in extracting plant matter. The non-volatile fractionis mixed with the plant matter, with extraction by stirring for aboutten minutes. Preferably, extraction is conducted at 50 degrees C. Invarious embodiments, extraction can be at about 40° C., about 45° C.,about 50° C., about 55° C., about 60° C., about 65° C., about 70° C.,about 75° C., where the mixture is held at this temperature for about 5minutes, about 10 min, about 15 min, about 20 min, about 25 min, about30 min, about 40 min, about 50 min, about 60 min, about 90 min, and soon. In addition to the above extraction period, the process ofextraction can include a ramping-up period, for example, a ten minuteperiod where the temperature of the mixture is ramped up from roomtemperature to about 50° C. Efficient extraction can be provoked bystirring, sonicating, rocking, tumbling, rotating in a manner thatproduces a vortex, and so on.

Following extraction, the entire mixture is then strained, for example,using a nylon straining bag, resulting in an oil that is free of visibleplant matter. Following extraction and before straining, the mixture isoptionally cooled, for example, to room temperature. The once-extractedplant matter can be re-extracted with an unused aliquot of thenon-volatile fraction derived from canola oil, resulting in a 2-foldextraction of the plant matter. Alternatively, or in addition, residualextract that is mixed with the plant matter can be removed andcollected, using an auger-type oil extruder.

Centrifugation and Heating in Vacuum Oven

After separation from the extracted plant matter, the oil is clarifiedby centrifuging at 3,000 rpm for ten minutes. The pellet is discarded,and the supernatant is retained. Alternatively, clarification can be atabout 3,000 rpm for about 20 minutes, 30 min, 40 min, 60 min, 80 min,100 min, 120 min, and so on. Also, clarification can be at about 4,000rpm, 5,000 rpm, 6,000 rpm, 10,000 rpm, for about 20 minutes, 30 min, 40min, 60 min, 80 min, 100 min, 120 min, and so on. The clarified oil issubjected to heating in a vacuum oven at 115 degrees C., for 710minutes. The most volatile compounds, such as monoterpenes are removed.Optionally, heating in the vacuum oven is conducted under conditions oftemperature and timing that can lead to decarboxylation of THC-acid toTHC. Centrifugation can be batchwise or continuous.

For any step in the present disclosure, vacuum can be either a completevacuum, or a partial vacuum that is 0.9 atmospheres, 0.8, 0.7, 0.6, 0.5,0.4, 0.3, 0.2, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.005, 0.004, 0.003,0.002, 0.001, 0.005, 0.0004, 0.0003, 0.0002, 0.0001, 0.00005, 0.00004,0.00003, 0.00002, 0.00001 atmospheres, and so on.

Distilling Step and Re-Distilling Step

Following vacuum oven treatment, the oil is then subject to distillationunder a vacuum. Distillation is conducted at 175 degrees C., or less, inorder to provide the final product of interest. In various embodiments,distillation is at about 140° C., about 145° C., about 150° C., about155° C., about 160° C., about 165° C., about 170° C., about 175° C.,about 180° C., about 185° C., about 190° C., about 200° C., and so on.In exclusionary embodiments, the present disclosure can exclude anyprocess, or can exclude any step, that involves distillation at atemperature that is above 180° C., about 185° C., above 190° C., above195° C., above 200° C., above 205° C., above 210° C., and so on.

Non-limiting examples of the final product of interest can be, forexample, a cannabinoid rich fraction with a content of about 65-75percent THC. The final product can be subject to another distillationstep, for example, at 165 degrees C., to yield a final product ofinterest that with a content of about 70-90 percent THC. There-distilling step can be at about 140° C., about 145° C., about 150°C., about 155° C., about 160° C., about 165° C., about 170° C., about175° C., about 180° C., about 185° C., about 190° C., about 200° C., andso on.

Depletion of Hentriacontane and of Other Chemical Constituents

With a vacuum oven treatment followed by a distillation step, thedesired product is an oil, that is optionally depleted in one or more ofpentadecanone, octacosane, hentriacontaine, and eicosane. Depletion ofhentriacontaine, for example, can result in a clarified oil thatcontains less than 80% of that present in the oil immediately prior tovacuum oven treatment, less than 70%, less than 60%, less than 50%, lessthan 40%, less than 30%, less than 20%, less than 10%, less than 5%,less than 2%, and so on, of that present in the oil immediately prior tovacuum oven treatment. In other embodiments, the product immediatelyafter vacuum oven treatment is depleted in octacosane, to one of theabove-disclosed percentages, depleted in pentadecanone, to one of theabove-disclosed percentages, depleted in eicosane to one of the abovepercentages, and any combination thereof. Content can be in terms ofpercentage that a given chemical has, in terms of weight of the chemicalcompared to weight of the entire oil. Methods for detecting andquantitating pentadecanone, octacosane, hentriacontaine, and eicosaneinclude, gas chromatography (GC), HPLC, GC-mass spectrometry (GC-MS),gas chromatography-olfactometry (GC-O) (Meyre-Silva et al (1998)Phytomedicine. 5:109-113; Usami et al (2013) J. Oleo Sci. 62:563-570;Kuwayama et al (2008) Forensic Sci. Int. 175:85-92).

Process Steps

Methods of the present disclosure can include one or more of theindicated series of steps. In some embodiments, the ordering of thesteps is mandatory, while in other embodiments, the ordering of one ormore of the steps can be reversed or changed. Any numbers, includingweights, volumes, percentages, and times can be varied to producedesired results, as would be understood by a person having ordinaryskill in the art.

Step i. Low-THCA canola oil is contacted to extracted plant matter. Thecombination is stirred at low heat for 10 minutes.

Step ii. The materials are filtered in a wine press through a fine nylonstraining bag, to produce a product and a by-product. The product is afirst preparation of canola oil with medium content of THCA, and theby-product is extracted plant matter with residual canola oil.

Step iii. The by-product is processed with an auger-type oil expeller.

Step iv. The product of Step (iii) is a second preparation ofmedium-THCA canola oil, and the by-product is a dry plant matter pelletthat contains less than 5% THCA. In alternate, embodiments, the pelletcontains less than 10% THCA, less than 8% THCA, less than 6% THCA, lessthan 4% THCA, less than 2% THCA, less than 1.0% THCA, or less than 0.5%THCA, and so on.

Step v. The first preparation of canola oil is combined with themedium-THCA content and second preparation of medium-THCA canola oil,where the combination is, “combined medium-THCA canola oil.”

The following step (Step vi) is an optional step, where canola oil thatalready contains a moderate quantity (or moderate concentration) of THCAis mixed with an unextracted plant matter, e.g., cannabis, where theresult is canola oil that is further enriched in THCA. The canola oilthat is further enriched in THCA may be referred to as, “high-THCAcanola oil.”

Step vi. The medium-THCA canola oil is combined with fresh plant matter(e.g., fresh cannabis). The combination is filtered in a wine pressthrough a fine nylon straining bag, resulting in a product that ishigh-THCA canola oil, and a by-product that is extracted plant matterthat contains residual canola oil.

The following step (Step vii) is an optional step.

Step vii. The high-THCA canola oil is subjected to a decarboxylationstep, where decarboxylation is provoked by heating in a vacuum oven, byheating with an in-line heat exchanger, or by heating by other relevantmethods.

The following step (Step viii) is an optional step.

Step viii. The high-THCA canola oil, where treated with a step dedicatedto provoking decarboxylation, or where not treated with a step dedicatedto provoking decarboxylation, is optionally further processed bycentrifugation to remove small particles and debris. The productresulting from this step is “high-THC canola oil.” The presentdisclosure provides compositions and methods, where canola oil is thenon-solvent, where canola oil mixed with another non-solvent is used, orwhere a non-solvent that does not comprise canola oil is used. Forexample, the non-solvent can be soy oil, corn oil, sunflower oil, sesameoil, safflower oil, olive oil, any mixture thereof, and the like. Thenon-solvent may comprise an ionic liquid, such as tributylmethylammoniummethyl sulfate. The non-solvent may comprise an imidazolium salt, suchas 1-butyl-3-methylimidazolium chloride.

Equipment for Purifying and Detecting Chemical Constituents

Cannabinoids can be separated, purified, analyzed, and quantified by anumber of techniques. Available equipment and methods include, e.g., gaschromatography, HPLC (high pressure liquid chromatography, highperformance liquid chromatography), mass spectrometry, time-of-flightmass spectrometry, gas chromatography-mass spectrometry (GC-MS), andliquid chromatography-mass spectrometry (LC-MS). Equipment forseparation and analysis is available from, e.g., Waters Corp., Milford,Mass.; Agilent, Foster City, Calif.; Applied Biosystems, Foster City,Calif.; Bio-Rad Corp., Hercules, Calif.). Equipment for scaled-upprocesses include rotary evaporators, heat exchangers, driers, andviscosity processors, and are available from, Buchi Corp., New Castle,Del.; Wolverine Tube, Inc., Decatur, Ala.; GEA Heat Exchangers, 44809Bochum, Germany; LCI Corp., Charlotte, N.C. Pumps and other equipmentare available from Grainger, Inc., Lake Forest, Ill. The methods,equipment, and compositions of the present disclosure can include, or bemanufactured with, expelling oil with an auger-type oil expeller,drying, and pelleting. Oil expellers are available, e.g., from IBGMonforts Oekotec, Nordrhein-Westfalen, Germany; and Nebraska ScrewPress, Lyons, Nebr.

The present disclosure provides in-line monitoring of purification, thatis, quantitation of THC as well as quantitation of impurities. In-linemonitoring may be by UPLC methods, or by other methods. Ultra-highperformance liquid chromatography (UPLC) is similar to HPLC, except thatUPLC uses smaller particles in the column bed, and greater pressures.The particles can be under 2 micrometers in diameter, and pressures canbe nearly 15,000 psi. UPLC also uses higher flow rates, and can providesuperior resolution and run times in the range of under 30 seconds (Wrenand Tchelitcheff (2006) J. Chromatography A. 1119:140-146; Swartz, M. E.(May 2005) Separation Science Redefined). The application of UPLC tocannabinoids has been described (see, e.g., Jamey et al (2008) J.Analytical Toxicology. 32:349-354; Badawi et al (2009) ClinicalChemistry 55:2004-2018). Suitable UPLC columns for cannabinoid analysisinclude, e.g., Acquity® UPLC HSS T3 C18 (100 mm×2.1 mm, 1.8micrometers), and Acquity® UPLC BEH C18 column (100 mm×2.1 mm, 1.7micrometers) (Waters, Milford, Mass.). Other methods for detectingcannabinoids include, e.g., infrared (IR) spectroscopy, gaschromatography mass spectroscopy (GCMS), and electrospray tandem massspectroscopy (ESI-MS/MS) (Ernst et al (2012) Forensic Sci. Int.222:216-222).

Crude Extracts

The present disclosure provides use of various forms of other botanicalextraction products initially made by other extraction methods. Otherextraction methods may involve a solvent, such as butane, hexane,methanol, alcohol, water or non-solvent based sub-critical CO₂, orsuper-critical CO₂ or other gas in a similar critical-type extractionmethod. These methods of extraction remove chemical constituents fromthe plant materials, for example, a mixture of both desired chemicalsand non-desired chemicals, where the removed substance takes the form ofan oil that typically, is a viscous oil. The resulting oil can bediluted into vegetable oil, and then be processed by a distillationapparatus.

Carbon dioxide is in its supercritical fluid state when both thetemperature and pressure equal or exceed the critical point of 31degrees C. and 73 atmospheres. In its supercritical state, CO₂ has bothgas-like and liquid-like qualities, and it is this dual characteristicof supercritical fluids that provides the ideal conditions forextracting compounds with a high degree of recovery in a short period oftime. Supercritical fluid extraction devices are available from, e.g.,Natex Prozesstechnologie, 2630 Ternitz, Austria; Jasco AnalyticalInstruments, Easton, Md.; Supercritical Fluid Technologies, Inc.,Newark, Del.

Without implying any limitation, the ratio (dry wt./dry wt.) of thenon-solvent/plant matter, immediately prior to extraction of the plantmatter, is greater than 100/1 (dry wt./dry wt.), or about 100/1 (drywt./dry wt.), 90/1, 80/1, 70/1, 60/1, 50/1, 40/1, 30/1, 20/1, 15/1,10/1, 9/1, 8/1, 7/1, 6/1, 5/1, 4/1, 3/1, 2/1, 1/1, and so on. Inembodiments, the ratio (dry wt./dry wt.) of the non-solvent/plantmatter, immediately prior to extraction of the plant matter, is about1/0.9, 1/0.8, 1/0.7, 1/0.6, 1/0.5, 1/0.4, 1/0.3, 1/0.2, 1/0.1 and so on.Also encompassed, are ratio ranges, such as the range ofnon-solvent/plant matter from 20/1 to 5/1, or the range ofnon-solvent/plant matter from 2/1 to 1/0.5.

Methods of the present disclosure can begin with an extract from plantmatter, such as a plant that is a member of the cannabaceae, forexample, cannabis. Where the extract is from cannabis, and where thecannabis was extracted with canola oil, the result is a high THC canolaoil. The high THC canola oil is then subject to distillation, such asbulk distillation, resulting in various fractions. These fractions mayinclude a fraction that is greater than 70% THC, a low THC fraction incanola oil, and a medium THC fraction in canola oil. In this method, themedium THC fraction in canola is subject to an additional round ofdistillation, in order to obtain a fraction that is high in THC anddepleted in canola oil.

Purified Compounds

The present disclosure provides by way of example only and not implyingany limitation in any way, methods for purifying cannabinoids includingspecific temperatures, timing, and so on. Methods for purifying thefollowing cannabinoids, without limitation, are provided by the presentdisclosure. Some examples of cannabacea, and their classification, areas follows: Aphananthe Planchon (syn. Mirandaceltis Sharp); Cannabis L.;Celtis L. (hackberries) (syn, Sparrea Hunz. & Dottori); Gironnieragaudich. (syn. Helminthospermum thwaites, Nematostigma Planchon);Humulus L. (hops) (syn. Humulopsis. grudz.); Lozanella Greenman;Parasponia Miguel; Pteroceltis Maxim; Trema Loureiro (syn. Sponiadecaisne); Lozanella; Parasponia; Pteroceltis. The present disclosureprovides methods for purifying compounds and chemicals from each ofthese cannabaceae. The disclosure also provides purified chemicalconstituents, chemical compositions, compounds, and chemicals, that areprepared by these methods.

The disclosure provides chemical compositions that comprisecannabinoids, that comprises cannabinoids but not terpenes, thatcomprise terpenes but not cannabinoids, and the like. Without implyingany limitation, the present disclosure encompasses a method whereterpenes are volatilized at a lower temperature, in order to separateterpenes from cannabinoids, followed by increasing the temperature tovolatilize cannabinoids, in order to produce a batch of terpenes and abatch of cannabinoids. In another method, both terpenes and cannabinoidsare first volatilized together at a higher temperature, followed bycollecting the batch that contains both terpenes and cannabinoids,followed by separating the terpenes from the cannabinoids, e.g., byheating.

“Plant matter that is derived from cannabaceae” refers, without implyingany limitation, to freshly harvested cannabaceae, sun-dried cannabaceae,chopped cannabaceae, ground cannabaceae, powdered cannabaceae,cannabaceae that is dried and chopped or ground or powdered (wheredrying is before or after being chopped, ground, or powdered),cannabaceae that comprises fungus or mold, and so on.

Where a chemical composition does not comprise cannabinoids, this canrefer to a chemical composition where less than 5.0%, less than 2.0%,less than 1.0%, less than 0.5%, less than 0.2%, less than 0.1%, lessthan 0.05%, less than 0.02%, less than 0.01%, less than 0.005%, lessthan 0.002%, less than 0.001%, less than 0.0005%, less than 0.0002%,less than 0.0001%, and so on (by weight), are cannabinoids. Where achemical composition does not comprise terpenes, this can refer to achemical composition where less than 5.0%, less than 2.0%, less than1.0%, less than 0.5%, less than 0.2%, less than 0.1%, less than 0.05%,less than 0.02%, less than 0.01%, less than 0.005%, less than 0.002%,less than 0.001%, less than 0.0005%, less than 0.0002%, less than0.0001%, and so on (by weight), are terpenes.

General chemical reagents, as well as cannabinoids, are available (SigmaAldrich, St. Louis, Mo.; Fischer Chemicals, Fair Lawn, N.J.; Cerilliant,Round Rock, Tex.; Promochem, Molsheim, France, Cayman Chemical Co., AnnArbor, Mich.). Purification can be followed by spiking an extract with alabeled cannabinoid. Useful labels include 33P, 35S, 14C, 3H, stableisotopes, fluorescent dyes, or fluorettes (see, e.g., Rozinov and Nolan(1998) Chem. Biol. 5:713-728).

Heat-Induced Decarboxylation

Decarboxylation of cannabinoids can be induced by heating. Cannabinoidacids can decarboxylate to the corresponding cannabinoids. For example,cannabidiolic acid can decarboxylate to produce cannabidiol (Veress, etal (1990) J. Chromatography A. 520:339-347; Jung et al (2007) J. MassSpectrom. 42:354-360; Harvey (1990) J. Ethnopharmacol. 28:117-128).Alkaline conditions can accelerate the heat-induced decarboxylation ofcannabinoid acids (Auwarter et al (2010) Forensic Sci. Int. 196:10-13).Contacting cannabis biomass with gas at a temperature of 105-450 degreesC., and in particular at 105-225 degrees C., can provoke decarboxylationof cannabinoid acids to free cannabinoids. At 145 degrees C., forexample, about 95% of cannabinoid acid is decarboxylated in about 30minutes. Lower temperatures can be chosen to avoid thermal oxidation ofdelta-9-tetrahydrocannabinol (delta-9-THC) to CBN, and thermalisomerization of delta-9-THC to delta-8-tetrahydrocannabinol(delta-8-THC).

Cannabinoids that can be decarboxylated include THCA (to THC), CBGA (toCBG), and CBDA (to CBD). In one aspect of the disclosure, THCAdecarboxylation is at least 50%, at least 60%, at least 70%, at least80%, at least 90%, at least 95%, at least 98%, at least 99%, at least99.5%, at least 99.9%, and the like. In another aspect, CBGAdecarboxylation is at least 1%, at least 10%, at least 20%, at least30%, at least 40%, at least 50%, at least 60%, at least 70%, at least80%, at least 90%, at least 95%, at least 98%, at least 99%, at least99.5%, at least 99.9%, and so on.

In a non-limiting embodiment, the present disclosure volatilizes one ormore chemical constituents, such as cannabinoids, at a temperature of80-85 degrees C., 85-90 degrees C., 90-95 degrees C., 95-100 degrees C.,100-105 degrees C., 105-110 degrees C. 110-115 degrees C., 115-120degrees C., 120-125 degrees C., 125-130 degrees C., or at a temperatureof 80-90 degrees C., 85-95 degrees C., 90-100 degrees C., 95-105 degreesC., 100-110 degrees C., 105-115 degrees C., 110-120 degrees C., 115-125degrees C., 120-130 degrees C., and so on. In exclusionary embodiments,the present disclosure excludes any method that volatilizes chemicalconstituents at above 95 degrees C., at about 98 degrees C., at above100 degrees C., at above 103 degrees C., at above 105 degrees C., atabove 108 degrees C., at above 110 degrees C., and so on.

Without implying any limitation, the present disclosure encompasses amethod that involves contacting a chemical constituent to a matrix, andcontacting a hot gas to the matrix, resulting in volatilizing one ormore chemical constituents from the matrix. The matrix can comprise, forexample, one or more of a porous ceramic, hollow fibers, glass wool,glass beads, celite, and the like. In exclusionary embodiments, thepresent disclosure can exclude any method, and any chemical constituentprepared by the method, that involves contacting a chemical constituentto a matrix. What can be excluded is any method that involves contactingan extract with a matrix, resulting in a matrix that is coated with theextract, and contacting a hot gas to the coated matrix, resulting involatilizing one or more chemicals or more or more chemical constituentsfrom the matrix.

In hot gas embodiments, the present disclosure encompasses one gas, suchas nitrogen, argon, carbon dioxide, helium, atmospheric air, watervapor, for use, for example, volatilizing a chemical constituent.Alternatively, the disclosure encompasses two hot gases such as amixture of nitrogen and carbon dioxide, nitrogen and water vapor, carbondioxide and water vapor, atmospheric air and nitrogen, atmospheric airand carbon dioxide, atmospheric air an argon, for example, forvolatilizing a chemical constituent. In another embodiment, thedisclosure encompasses three or more gasses, for example, forvolatilizing a chemical constituent.

In exclusionary embodiments, the present disclosure can exclude one gas,such as nitrogen, argon, carbon dioxide, helium, atmospheric air, watervapor, for use, for example, volatilizing a chemical constituent.Alternatively, the disclosure can exclude two hot gases such as amixture of nitrogen and carbon dioxide, nitrogen and water vapor, carbondioxide and water vapor, atmospheric air and nitrogen, atmospheric airand carbon dioxide, atmospheric air an argon, for example, forvolatilizing a chemical constituent. In another embodiment, thedisclosure can exclude three or more gasses, for example, forvolatilizing a chemical constituent.

By way of a non-limiting example, dry and homogenized cannabis can beextracted with methanol:chloroform (9:1, vol./vol.), and then subject todecarboxylation, by the following procedure. Dry and homogenizedcannabis can be extracted in the solvent by vortexing, followed bysonication in an ultrasonic bath, with repetition of the vortexingprocedure after 5 minutes, after 10 minutes, and again after 15 minutes.Solid plant matter can then be separated from the extract bycentrifugation. Decarboxylation can be accomplished as follows. Theresulting oil can then be decarboxylated by heating at 210 degrees C.for 15 minutes.

Decarboxylation Induced During Heat-Induced Vaporization

Cannabinoid acids present in a non-solvent extract can be decarboxylatedby a hot gas, with vaporization of the decarboxylated cannabinoids.Alternatively, cannabinoid acids present in the mixture of non-solventextract and plant matter can be decarboxylated by a hot gas, withvaporization of the decarboxylated cannabinoids. In heat-inducedvaporization, a hot gas is bubbled through the extract (or mixture ofplant matter and the non-solvent) resulting in decarboxylation andvaporization. The gas can be, for example, atmospheric air, nitrogen,argon, or any combination thereof. The temperature of the gas can be,for example, less than 100 degrees C., 100-110 degrees C., 110-130degrees C., 130-150 degrees C., 150-170 degrees C., 170-190 degrees C.,180-200 degrees C., 190-210 degrees C., 200-220 degrees C., 210-230degrees C., 220-240 degrees C., 230-250 degrees C., 240-260 degrees C.,and so on. Following bubbling, the vapor can be bubbled through a secondnon-solvent that has a controlled, cool temperature, in order to collectthe decarboxylated cannabinoids. This method of heat-induceddecarboxylation, when carried out with the mixture of non-solventextract and plant matter, can avoid steps of centrifugation, filtering,or both centrifugation and filtering that are needed to remove extractedplant matter and other solid residues.

Decarboxylation can be achieved by contacting the extract containingcannabinoid acids with a hot surface. For example, decarboxylationoccurs when contacting an enriched non-solvent vegetable oil solution toa surface with a temperature of 70 degrees C. higher than the solutionfor a period of 60 minutes. In other embodiments, the temperaturedifferential can be higher than 80 degrees C., higher than 90 degreesC., higher than 100 degrees C., higher than 110 degrees C., higher than120 degrees C., higher than 130 degrees C., higher than 140 degrees C.,or higher than 150 degrees C. Contact times with the hot surface can beabout 1 minute, 2 minutes, 5 minutes, 10 minutes, 15 minutes, 30minutes, 60 minutes, 90 minutes, 120 minutes, or the like.

Other methods of decarboxylation involve the use of an oven or otherheating apparatus. Higher heat generally equates to a faster rate ofdecarboxylation.

Lipid Compositions

The present disclosure provides non-solvent lipid compositions for useas an extraction agent, for use as a carrier, or for use as both anextraction agent and as a carrier, for processing chemical constituentsand for serving as a vehicle for dissolving said chemical constituents.The lipid composition can be, canola oil, peanut oil, sunflower oil,safflower oil, corn oil, soy oil, sesame oil, olive oil, avocado oil,grapeseed oil, mulatto oil, almond oil, mustard oil, walnut oil, seedoil, nut oil, ground nut oil, a tree oil, jojoba oil, guayule oil, fishoil, cod liver oil, oil from a recombinant plant or from a recombinantmicroorganism, or any combination thereof, and the like. Also available,is an oil such as a wax oil, that is not a triglyceride oil. Moreover,the lipid composition can be a fat that is normally a solid at roomtemperature, and where extraction occurs at or above the meltingtemperature of the fat. The fat can be, for example, butter, margarine,lard, hydrogenated vegetable oil, partially hydrogenated vegetable oil,any combination thereof, and the like. Furthermore, the lipidcomposition can be a combination of an oil and a fat, such as acombination of canola oil and butter. What is encompassed isplant-derived oils, fungus-derived oils, animal-derived oils,microorganism-derived oils, oils manufactured by recombinantmicroorganisms or recombinant algae and the like.

Prior to use, the carrier lipid composition is subject to a purificationscheme. Purification can be accomplished with distilling under vacuum(0.001 mbar) at higher temperatures (195 degrees C.). Preferred vacuumis a vacuum of 0.001 torr, or a more intense vacuum, Regarding units, itis the case that 1 mbar equals 0.750 torr. A goal is to ensure that thechemical constituents provided by the present methods and systems do notcontain residues from the vegetable oil, or from any other lipidcomposition that is used. The method keeps the highest boiling portionsto use for the extraction, as these portions need to be higher inboiling point than the chemical constituents of interest in and on theplant.

In an alternative embodiment, distillation is conducted at atmosphericpressure (and not under any partial vacuum). Atmospheric pressures fordistillation can lead to the ability to select alternative fractionateswhere it is desired to only fractionate out light boiling chemicalconstituents.

In exclusionary embodiments, the present disclosure can exclude anysystem, method, and composition, that involves a solvent, a solvent thatis at least 95% pure, a solvent that is at least 99% pure, and the like,such as acetone, an ether, dimethyl ether, diethyl ether, an alcohol,methanol, ethanol, propanol, isopropanol, methylene chloride,chloroform, or any combination thereof, and so on. In exclusionaryembodiments, what can also be excluded is any system, method, andcomposition, prepared with the use of butter, margarine, lard, fish oil,hydrogenated vegetable oil, partially hydrogenated vegetable oil, andthe like. In other exclusionary embodiments, what can be excluded is anysystem, method, or composition, that is prepared with or that contains,a seed oil, a nut oil, a ground nut oil, a tree nut oil, canola oil,peanut oil, sunflower oil, safflower oil, corn oil, soy oil, sesame oil,olive oil, or any combination thereof, and the like.

What can be excluded is an extraction procedure, where extraction iswith a mixture of solvent and non-solvent. Also, what can be excluded isan extraction procedure, where extraction with a solvent is followed byextraction with a non-solvent, or where extraction with a non-solvent isfollowed by extraction with a solvent. What can be excluded, forexample, is an extraction procedure where extraction is with vegetableoil/methanol (10%/90%) vegetable oil/methanol (20%/80%) by weight),vegetable oil/methanol (40%/60% by weight), vegetable oil/methanol(50%/50% by weight), vegetable oil/methanol (80%/20% by weight),vegetable oil/methanol (90%/10% by weight), and so on.

What can be excluded, for example, is an extraction procedure whereextraction is with vegetable oil/methylene chloride (20%/80% by weight),vegetable oil/methylene chloride (40%/60% by weight), vegetableoil/methylene chloride (50%/50% by weight), vegetable oil/methylenechloride (80%/20% by weight), vegetable oil/methylene chloride (90%/10%by weight), and so on.

Also provided, is an extraction procedure that uses a non-solvent suchas canola oil, where the extraction is with a liquid that is a mixtureof non-solvent and solvent. The mixture can take the form, on a percentweight basis, of about 95% non-solvent/5% solvent, about 90%non-solvent/10% solvent, about 85% non-solvent/15% solvent, about 80%non-solvent/20% solvent, about 75% non-solvent/25% solvent, about 70%non-solvent/30% solvent, and the like. The above methods and mixturescan also be exclusionary.

Location of the Step of Heat-Induced Decarboxylation in the ProcessScheme

Heat-induced decarboxylation can be performed on non-extracted plantmatter. However, it is preferred to perform heat-induced decarboxylationon the non-solvent extract, because the extract has a smaller volumethan the plant matter, and also because the presence of plant matter isexpected to generate off-flavors or off-odors. Heat-induceddecarboxylation is preferably conducted before distillation (or otherprocess step involving pressure and heating), because anydecarboxylation that occurs inside a distillation apparatus coulddisrupt the vacuum, resulting in inefficient distillation, for example,taking the form of bumping.

Recovery

One hundred percent (100%) of cannabinoids can be defined as the totalamount, in terms of moles, that is initially present in thenon-extracted plant matter. Alternatively, 100% can be defined as thetotal amount, in terms of moles, that is initially present in thenon-solvent extract. In yet another alternative, 100% can be defined asthe total amount, in terms of moles, that is present at the beginning ofany given process step. In a preferred embodiment, the final product ofthe present disclosure takes the form of a cannabinoid-rich resin. Thiscannabinoid-rich resin can optionally be redistilled to achieve higherpurity. Redistillation is preferably at 165 degrees C., where the resultis a resin containing THC at a purity of greater than 80%.

Reductions in the proportion of non-solvent, such as a vegetable oil,are desired. Inhaled vegetable oils can result in a disorder called,“exogenous lipoid pneumonia” (Annobil et al (1997) Trop. Med. Int.Health. 2:383-388; Hoffman et al (2005) Arch. Pediatr. Adolesc. Med.159:1043-1048; Betancourt et al (2010) Am. J. Roentgenol. 194:103-109).

In embodiments, cannabinoid purity is greater than 70%, greater than75%, greater than 80%, greater than 85%, greater than 90%, greater than95%, greater than 96%, greater than 97%, greater than 98%, greater than99%, greater than 99.5%, where the percent can be in terms of weight ofcannabinoid as a percentage of weight of the resultant oil, where thepercent of cannabinoid can be in terms of moles of cannabinoid moleculesas a percentage of moles of the total molecules.

Recovery of the cannabinoids can be measured after each process step.Where applicable, recovery can also be measured after each reiterationof a process step that is repeated.

Overall recovery can refer to the difference between the number of molesof cannabinoids that is initially extracted with the non-solventextracting reagent, and the final purified product. Alternatively,overall recovery can refer to the difference between the number of molesof cannabinoids in the non-extracted plant matter, and the finalpurified product.

In embodiments, the overall recovery can be at least 99%, at least 98%,at least 97%, at least 96%, at least 95%, at least 90%, at least 85%, atleast 80%, at least 75%, at least 70%, at least 65%, at least 60%, atleast 55%, at least 50%, at least 45%, at least 40%, at least 35%, atleast 30%, at least 25%, at least 20%, at least 15%, at least 10%, andthe like. Where aliquots of sample are withdrawn from the process, atone or more steps, the recovery is corrected for the amount withdrawn.Aliquots can be withdrawn for analysis, for quality control, or forstorage.

An alternative method for calculating recovery, is to factor in areduction in recovery, where one or more cannabinoids have been found tobe converted to a non-desirable entity, such as to a cannabinoid that isisomerized, oxidized, oxidized to create an aldehyde, ring opened,condensed with another cannabis-derived chemical constituent, condensedwith a component of the non-solvent extracting agent, or otherwisedestroyed. In other words, where 5% of the moles of cannabinoid havebeen found to be oxidized to an aldehyde, the calculated recovery can beproportionately reduced.

Rate-Limiting Step

The present disclosure provides a multi-step processes that avoids, orreduces, the tendency of any given step to be a rate-limiting step. Forexample, in a multi-step process that processes 100 grams of cannabinoidper hour (overall production, as measured immediately after the finalstep), the process can be operated to minimize accumulation ofcannabinoids immediately before a given intermediate step that isidentified as potentially a rate-limiting step. The methods of thepresent disclosure can be adjusted, to minimize accumulation ofcannabinoids immediately before the potential rate-limiting step atunder 20 grams cannabinoid per hour, under 15 grams, under 10 grams,under 5 grams, under 4 grams, under 3 grams, under 2 grams, under 1gram, under 0.5 grams, under 0.2 grams, under 1 gram, under 0.5 grams,under 0.2 grams, under 0.1 grams, and so on. As stated above, this iswith regard to a multi-step process that produces a composition at arate of 100 grams of cannabinoid per hour. In non-limiting embodiments,this 100 grams of cannabinoid may be at least 70% pure, at least 80%pure, at least 90% pure, at least 95% pure, at least 98% pure, and soon.

The term “accumulation” refers to cannabinoid that piles up immediatelybefore that step, resulting in a delay or hold-up of flow of chemicalconstituents through subsequent steps. Expressed another way, the methodmaintains a ceiling of cannabinoid accumulation at under 20%, under 15%,under 10%, under 5%, under 2%, under 1%, under 0.5%, under 0.2%, under0.1%, and so on, with respect to the “100%” that is defined above, Torepeat, the term “accumulation” does not refer to the total amount ofcannabinoid that passes through a given step per hour, but instead, itrefers to the amount that piles up at that given step, resulting in aslight delay (or perhaps in a more lengthy delay) in processing of thecannabinoid through subsequent steps.

Exclusionary Embodiments

Without implying any limitation, the present disclosure can exclude anymethod that extracts plant matter with an alcohol (e.g., methanol,ethanol, isopropanol), that extracts plant matter with supercriticalfluid carbon dioxide, that extracts plant matter with a non-aqueoussolvent, that extracts plant matter with, e.g. dichloromethane, hexane,ether, and so on. What can also be excluded is any method that uses acyclone separator, or any method where heat-induced decarboxylation isperformed on non-extracted plant matter, or where heat-induceddecarboxylation is performed prior to extraction of plant matter.

Processes

Following removal of the spent plant matter, the extract can be heatedin order to provoke heat-induced decarboxylation of cannabinoids.Alternatively, the step of heating can be carried out at an earlier panof the scheme, where the extract is subjected to beating in order tovolatilize the cannabinoids, where decarboxylation occurs during thisheating, and where the volatilized cannabinoids are then captured usinga condenser. In a preferred but non-limiting embodiment, the volatilizedcannabinoids are condensed and captured by drawing through canola oil,where the canola oil is at or below room temperature. Once captured, thecannabinoids can be: (1) Considered to be the final product, (2) Thecannabinoids can be dispersed into a non-solvent such as canola oil andthen optionally subjected to further purification, or (3) Thecannabinoids can be subject to further purification. At the end of theprocess, the used canola oil can be utilized again for extracting plantmatter.

In one embodiment, the starting material is canola oil that has a highcontent of THC. The high-THC canola oil is optionally subjected todistillation. Immediately after processing by the distillation step, theproducts are medium-THC canola oil, low-THC canola oil, and aTHC-composition that is greater than 50% THC. The medium-THC canola oilcan be re-processed by distillation.

Further, each of the various elements of the invention and claims mayalso be achieved in a variety of manners. This disclosure should beunderstood to encompass each such variation, be it a variation of anembodiment of any apparatus embodiment, a method or process embodiment,or even merely a variation of any element of these.

Particularly, it should be understood that as the disclosure relates toelements of the invention, the words for each element may be expressedby equivalent apparatus terms or method terms—even if only the functionor result is the same.

Such equivalent, broader, or even more generic terms should beconsidered to be encompassed in the description of each element oraction. Such terms can be substituted where desired to make explicit theimplicitly broad coverage to which this invention is entitled.

It should be understood that all actions may be expressed as a means fortaking that action or as an element which causes that action.

Similarly, each physical element disclosed should be understood toencompass a disclosure of the action which that physical elementfacilitates.

Any patents, publications, or other references mentioned in thisapplication for patent are hereby incorporated by reference.

Finally, all references listed in the Information Disclosure Statementor other information statement filed with the application are herebyappended and hereby incorporated by reference; however, as to each ofthe above, to the extent that such information or statementsincorporated by reference might be considered inconsistent with thepatenting of this/these invention(s), such statements are expressly notto be considered as made by the applicant.

In this regard it should be understood that for practical reasons and soas to avoid adding potentially hundreds of claims, the applicant haspresented claims with initial dependencies only.

Support should be understood to exist to the degree required under newmatter laws—including but not limited to 35 USC § 132 or other suchlaws—to permit the addition of any of the various dependencies or otherelements presented under one independent claim or concept asdependencies or elements under any other independent claim or concept.

To the extent that insubstantial substitutes are made, to the extentthat the applicant did not in fact draft any claim so as to literallyencompass any particular embodiment, and to the extent otherwiseapplicable, the applicant should not be understood to have in any wayintended to or actually relinquished such coverage as the applicantsimply may not have been able to anticipate all eventualities; oneskilled in the art, should not be reasonably expected to have drafted aclaim that would have literally encompassed such alternativeembodiments.

Further, the use of the transitional phrase “comprising” is used tomaintain the “open-end” claims herein, according to traditional claiminterpretation. Thus, unless the context requires otherwise, it shouldbe understood that the term “comprise” or variations such as “comprises”or “comprising”, are intended to imply the inclusion of a stated elementor step or group of elements or steps but not the exclusion of any otherelement or step or group of elements or steps.

Such terms should be interpreted in their most expansive forms so as toafford the applicant the broadest coverage legally permissible.

It should also be understood that a variety of changes may be madewithout departing from the essence of the invention. Such changes arealso implicitly included in the description. They still fall within thescope of this invention. It should be understood that this disclosure isintended to yield a patent covering numerous aspects of the inventionboth independently and as an overall system and in both method andapparatus modes.

While the system, compositions, and methods, have been described interms of what are presently considered to be the most practical andpreferred embodiments, it is to be understood that the disclosure neednot be limited to the disclosed embodiments. It is intended to covervarious modifications and similar arrangements included within thespirit and scope of the claims, the scope of which should be accordedthe broadest interpretation so as to encompass all such modificationsand similar structures. The present disclosure includes any and allembodiments of the following claims.

Example 1

The following example outlines a decarboxylation trial performed usingthe methods and systems of the present disclosure. The goal of the trialwas to decarboxylate THCA to THC at 145 degrees C. for 10 minutesexposure time. An in-line decarboxylation pipe with a total internalsurface area was approximately 46.8 in² was utilized.

A pump drive forces the material of interest, such as THCA-enrichedcanola oil, through the apparatus at a rate of 10 mL/min. The apparatuswas heated with heating fluid of constant temperature. For the presenttrial, the heating fluid was set to 200 degrees C. Thermocouples at theinlet and outlet measured the temperature of the material of interestbefore decarboxylation and after. The average inlet temperature was 77.2degrees C., and the average outlet temperature was 149.3 degrees C., asmeasured by the thermocouples.

The collection vessel was situated on a stir plate, so that stirringcould be used to ensure homogeneity of the collected solution.

An initial volume of 250 mL of THCA-enriched canola oil was transferredto the collection vessel. The material was measured for THC and THCAprior to decarboxylation. The starting level of THC was 21.91 mg/g; andthe starting level of THCA was 11.05 mg/g. The material was recirculatedthrough the apparatus at the rate of 10 mL/min as determined by thepump. Each theoretical pass of 250 mL through the apparatus thereforerequired 25 minutes.

THC and THCA levels in the material were measured at intervals of 25-30minutes. At each interval, a sample of material was taken directly fromthe outlet. In addition to the initial measurement at t=0, twelvetheoretical passes were measured, for a total experiment time ofapproximately 354 minutes. The experimental results are displayed inTable 1 and in the corresponding graph in FIG. 4.

TABLE 1 Time Unk.Deg. THC THCA Sample (m) THC % THCA % CBN % % [mg/g][mg/g] % Decarbed 1 0 2.191 1.105 0.216 0.215 21.91 11.05 49.56 2 292.707 0.076 0.211 0.276 27.07 0.76 97.19 3 58 2.844 0 0.213 0.267 28.440 100 4 87 2.867 0 0.227 0.292 28.67 0 100 5 116 2.979 0 0.238 0.2729.79 0 100 6 150 3.041 0 0.244 0.288 30.41 0 100 7 176 3.117 0 0.2520.276 31.17 0 100 8 205 3.18 0 0.256 0.241 31.8 0 100 9 234 3.151 00.273 0.259 31.51 0 100 10 260 3.185 0 0.275 0.26 31.85 0 100 11 2913.067 0 0.28 0.253 30.67 0 100 12 325 3.159 0 0.295 0.293 31.59 0 100 13354 3.136 0 0.301 0.271 31.36 0 100

Sample points 2-13 on the graph in FIG. 4 each represent one theoreticalrun of 25-30 minutes. The first sample point represents the materialbefore it was run through the apparatus. After the first 2 theoreticalruns, no concentration of THCA is detected. The absolute maximum THCconcentration measured in the experiment occurs after 10 theoreticalruns at 260 minutes. The second-highest measured THC concentration wasafter 7 theoretical runs at 176 minutes.

Example 2

Using an apparatus with greater surface area than the one described inExample 1, it is possible to decarboxylate more efficiently. In anotherexperiment using an in-line decarboxylation pipe having a total internalsurface area of 249.6 in² (or more than 5 times the internal surfacearea of the device of Example 1), decarboxylation efficiency increases.In this modified apparatus, one theoretical run at 10 mL/min creates 198seconds of exposure time. Factoring in an estimated 8.25 mL of deadvolume in the pipe, one theoretical run creates 49.5 seconds of exposuretime.

In the first theoretical run, 97.19% of the THCA was convened to THC.That is about double the efficiency of the device in Example 1, whereonly 49.56% of THCA was decarboxylated in the first run. The 97.19%decarboxylation equated to 2.367 g of THCA, or 6.602 mmol THCA in 37.2seconds of exposure time.

What is claimed is:
 1. A method for purifying one or more chemicalconstituents from plant matter; the method comprising: (i) contactingthe plant matter with a non-solvent to obtain a mixture of extractedplant matter and non-solvent enriched in one or more chemicalconstituents from the plant matter; and (ii) separating the non-solventenriched in one or more chemical constituents from the extracted plantmatter using an auger-type oil extractor; wherein the step of separatingthe non-solvent enriched in one or more chemical constituents comprisesdrawing hot gas through the non-solvent to obtain a volatilized fractionand a removed fraction.
 2. The method according to claim 1, wherein thenon-solvent is selected from the group consisting of plant oil, wax oil,fish oil, fruit oil, and a mixture thereof.
 3. The method according toclaim 1, wherein the non-solvent is tributylmethylammonium methylsulfateor 1-butyl-3-methylimidazolium chloride.
 4. The method according toclaim 1, wherein the one or more chemical constituents is separated fromthe non-solvent via volatilization.
 5. The method according to claim 4,wherein the step of volatilization results in the separation of a firstchemical constituent from a second chemical constituent.
 6. The methodof claim 4, wherein the step of volatilization results in one or morevolatilized fractions.
 7. The method according to claim 6, wherein theone or more volatilized fractions is enriched in one or morecannabinoids.
 8. The method according to claim 7, wherein the one ormore cannabinoids is selected from the group consisting of delta-9tetrahydrocannabinol, tetrahydrocannabinolic acid, cannabidiol, andcannabinol.
 9. The method according to claim 7, wherein volatilizationresults in the separation of a first cannabinoid from a secondcannabinoid.
 10. The method according to claim 6, wherein the one ormore volatilized fractions is depleted in one or more cannabinoids. 11.The method according to claim 1, wherein the step of separatingnon-solvent enriched in the one or more chemical constituents comprisescentrifugation or filtration.
 12. The method according to claim 1,further comprising condensing the volatilized fraction and the removedfraction to obtain a composition comprising the one or more chemicalconstituents.
 13. The method according to claim 1, wherein hot gasinduces decarboxylation of at least one heat-decarboxylatablecannabinoid.
 14. The method according to claim 1, wherein steps (i)-(ii)are repeated continuously.
 15. The method according to claim 1, whereinthe plant matter is in a form selected from the group consisting ofdried, chopped, ground and powdered.
 16. The method according to claim1, wherein the plant matter is selected from species in the Cannabaceaefamily.